Prenatal cocaine exposure during critical periods of development in rabbits selectively alters the structure of specific types of neurons and the coupling of the D1 dopamine (DA) receptor in DA-rich regions of the cerebral cortex, such as prefrontal and anterior cingulate cortices. Consistent with findings in this model system, children exposed to cocaine in utero exhibit a developmental phenotype that resembles attention deficit disorder. The specific expression patterns of the D1 receptor, changes in neurophysiological properties of cortical interneurons modulated by DA, and disrupted attention will be investigated in the rabbit model of in utero cocaine exposure. Pharmacological manipulations will establish a direct role of D1 receptor dysfunction in the poor performance on tasks that tap attention systems. Preliminary data suggest that in utero cocaine results in systems that function normally at baseline, but when the system is challenged, behavioral abnormalities emerge. Detailed characterization of the developmental consequences of prenatal cocaine exposure in this animal model will facilitate an understanding of the underlying molecular and cellular mechanisms that disrupt behavior in the clinical population.